First broadcast on September 12, 1992, the show ran for two seasons, spanning 26 episodes, before it left after the 1993-1994 season with Disney's acquisition of ABC. It also aired on YTV from 1992 to 1999 in Canada. The series was then broadcast on Toon Disney from 1998 to 2001.

Like many cartoons during its time, C.O.W.-Boys dealt with a mutation of some kind. In this case, an irradiated comet struck the late 19th century Western plains creating a miles high mesa shrouded in clouds. Everything trapped on top of the mesa was "cow-metized" by the light from the "cow-met" and "evolved" into a "bovipomorphic" state. Inspired by old tales of the Wild West, this new bovine community developed to the point where they emulated that era's way of life, including the requisite ruffians and corrupt sheriffs. However, their knowledge of Wild West living was limited, and as such, many things about their culture had to be improvised to 'fill in the blanks'. The concepts of steampunk and Weird West were utilized throughout its run.

The series focuses on trying to keep justice in the frontier territory. The lawbreakers were too much for the corrupt regulators of Cowtown - Mayor Bulloney and Sheriff Terrorbull - to handle by themselves. Helping them out, whether they wanted it or not, were a group of peacekeepers known as C.O.W.-Boys, short for "Code Of the West". Led by bull Marshal Moo Montana, the C.O.W.-Boys also included the Dakota Dude and the Cowlorado Kid. The muscle-bound Marshal and his deputies had their hands full with various ruffians and outlaw gangs that plagued the otherwise peaceful town.

Marshal Moo Montana (voiced by Pat Fraley) - Leader of the C.O.W.-Boys and marshall of Moo Mesa. Courageous and quick on his hooves, Moo Montana "battles the bad guys and makes the West a safer place to graze". Lives by the Code of the West, which he seems to make up as he goes along (episode "The Big Cow Wow"). His horse's name is Cyclone.

The Dakota Dude (voiced by Jim Cummings) - The soft-spoken muscle of Montana's posse, Dakota possesses a cool temperament and rarely gets mad, even in near-death experiences (as seen in "Dances with Bulls"). Dakota agreed to marry Cowlamity Kate in Wedding Bull Blues to save her father's inheritance. His horse's name in Rebel and is scared of heights.

Cowlorado Kid (voiced by Jeff Bennett) - The youngest of the group and a self-proclaimed ladies' man with a good singing voice, regardless of his skill with the lasso and guitar. Cowlorado isn't a deputy yet. In Stolen on the River, he tries to prove he's worthy of being a deputy by catching Five Card Cud only to get in trouble and be rescued by Dakota and Moo. His horse's name is Jezebel.

Lily Bovine (voiced by Charity James) - A bartender, former showgirl, and owner of the local saloon, The Tumbleweed. Lily is Moo Montana's love interest. Her best friend is Cowlamity Kate.

Cody Calf (voiced by Troy Davidson) - Nicknamed "Calf-Pint" by Moo and his posse, he idolizes the marshall and hopes to be a lawcow himself when he grows up. He is apparently related to Lily Bovine in some way and lives with her, though he does not appear to be her son; like everyone else, he refers to her as "Miss Lily". Though well-meaning, he often gets himself into serious trouble trying to "help" the lawcows, but has been a useful asset on several occasions.

Cowlamity Kate Cudster (voiced by Kay Lenz) - Tomboyish rancher and operator of the highly profitable Golden Cud Mine. She's as hard-working and hard-riding as any bull, and has enough skill with a lasso to put Cowlorado to shame. She returns Dakota's romantic feelings; she gave him the hat he wears and nearly married him in Wedding Bull Blues. Her name is a play on that of the famous Wild West heroine, Calamity Jane. (Voice: Kay Lenz).

J.R. (voiced by Michael Horse) - An Indianbison who occasionally aids Moo, Dakota, and Cowlorado if the situation needs it. He tends to ramble about the scientific principles of his inventions which the C.O.W.-Boys don't want to listen to.

Mayor Oscar Bulloney (voiced by Michael Greer) - The greedy and corrupt mayor of Cowtown in Moo Mesa, Bulloney rigs elections (as seen in Stolen on the River) and makes taxes so high that the Masked Bull compares it to stealing. He also serves as Cowtown's crooked Justice of the Peace and Bank President.

Sheriff Terrorbull (voiced by Joe Piscopo) Selected by the corrupt Bulloney, Terrorbull uses his sheriff's badge to conceal his evil intentions. When committing crimes, Terrorbull takes on the guise of the notorious outlaw called the Masked Bull. Curiously, Terrorbull has an upright posture as the Masked Bull while he is normally seen with a hunched back. He was forced to leave Cowtown after losing a bet to Moo in "No Face To Hide" to see who can catch Shock Holiday. Afterwards, Terrorbull became sheriff of the remote town of Lonesome Gulch as Mayor Bulloney tells him to put up with it until he can think of a way to get him back into Cowtown. At Lonesome Gulch, Sheriff Terrorbull continued his unlawful exploits.

Saddle Sore (voiced by Jim Cummings) - A scorpion and one of the comically inept henchmen of Sheriff Terrorbull. He is slightly smarter and braver than Boot Hill Buzzard, but only just.

Boot Hill Buzzard (voiced by Danny Man) - A buzzard who is Sheriff Terrorbull's other comically inept henchman of Sheriff Terrorbull. As the more dim-witted of the two, he is often saddled with more than his fair share of the grunt work, especially if the job involves something embarrassing or unappealing (such as cross-dressing). His name is taken from an old west slang term for a graveyard.

Cowtown dries up and only Mayor Bulloney has water. When Cody finds the real reason for this, it is up to him to bring water back everyone.

8

"Wedding Bull Blues"

When Cowlamity Kate doesn't receive a letter from her father who has been exploring the Mesa for 7 years, Mayor Bulloney claims he will be taking all her property since her father had no will. But when a page of one of her father's old letters shows up, stating Kate will inherit the ranch and his gold, though only if she is married, Kate plans to make Dakota her husband.

9

"Legend of Skull Duggery"

When Cody, Carly, and Jake find a treasure map in Cowlamity Kate's attic, they decide to follow it to find Tom Duggery's lost silver.

10

"Stolen on the River"

In an attempt to get his own deputy star, Cowlorado decides to catch Five Card Cud all by himself only to fail in a shot of embarrassment as he's rescued by Dakota and Moo.

11

"Dances with Bulls"

Moo and Terrorbull get in a mess when they both try to capture the Gila Hooligans.

12

"The Big Cow Wow"

Cody is really excited about going to the Pueblo's annual Cow-Wow with J.R. and Tejua, but a string of robberies by the Hole in the Ground Gang could disrupt the whole fiesta. When Moo and the other C.O.W.-Boys run into some trouble trying to catch the gang Cody and Tejua help to bring them to justice.

13

"Another Fine Mesa"

No one cares that it is Moo's 10th anniversary as marshal. Then, Moo receives a telegram from his hometown of Miller Glen where the retiring sheriff wants Moo to take over. Now Moo must decide between Miller Glen where he is beloved by the townsfolk, and Cowtown.

Many trains have been stolen by Shock Holiday's gang where Shock Holiday is holding them hostage until the Railroad President pays a huge ransom. When Marshall Moo fails at capturing the thief, Sheriff Terrorbull challenges him to see who catches the train thief first and the loser will have to leave Cowtown.

15

"The Down Under Gang"

Cow Belle and her sons have an underground hideout called Sidewinder City which allows other outlaws to use it in exchange of a share of what they steal. When Cowlorado Kid is captured during the infiltration, Moo Montana and Dakota Dude must find Sidewinder City and rescue him while also dealing with the Masked Bull.

16

"Cow Pirates of Swampy Cove"

The pirate captain Longhorn Silver and his band of buccaneers have been robbing trains and causing trouble on Moo Mesa's waterways. With a gold shipment and Cody's money for new boots in their possession, Moo Montana, Dakota Dude, and Cowlorado Kid have to go to Newportleans to track these pirates down. While trying to get back the money, Cody is caught by the Masked Bull as part of his plan to work with Longhorn Silver to dispose of the C.O.W.-Boys. Now the C.O.W.-Boys must rescue Cody, reclaim the stolen loot, and defeat Longhorn Silver.

17

"The Cacklin Kid"

Moo Montana, Dakota Dude, and Cowlorado Kid apprehend the Cacklin Kid after he was nearly disposed of by the Baying Bunch led by Scavenger who are seeking the location of where the Cacklin Kid hid the Baying Bunch's loot. At the courthouse, Cacklin Kid gets sympathy from Judge Overrule who instructs that Moo Montana, Dakota Dude, and Cowlorado Kid safely transports Cacklin Kid to the federal penitentiary to serve out his one year sentence. Now the C.O.W.-Boys must get the Cacklin Kid to the penitentiary safely while evading the Baying Bunch who have tricked Sheriff Terrorbull into helping them.

18

"Skull Duggery Rides Again"

Skull Duggery returns with an age accelerating spell.

19

"Billy the Kidder"

20

"How the West was Shrunk"

21

"Circus Daze"

The circus comes to town, but amusement of the masses is the last thing on the ringmaster's mind.

22

"No Way to Treat a Lady"

Moo Montana, Dakota Dude, and Cowlorado Kid have to deal with four masked outlaws who happen to be ladies.

In 1991, Hasbro Toys produced a series of ten action figures and one vehicle(IronHorse). Marshal Moo Montana was produced heaviest while the character Boot Hill Buzzard is the rarest of the set with only a limited number released. Of the three main heroes, the Dakota Dude is the scarcest.

In 1999, to coincide with the series being broadcast on the Toon Disney channel, the Kid Stuff company manufactured a set of 3" tall action figures for its Moo Mesa Kids Meal promotion. Articulated at the shoulders, neck, and waist, the assortment consisted of Marshal Moo Montana, The Dakota Dude, The Cowlorado Kid, Miss Cowlamity Kate, Cody Calf, and the Masked Bull. These were available at participating restaurants.

Archie Comics released both a mini-series and regular series of Wild West C.O.W.-Boys of Moo Mesa comic books. The first issue of the mini-series came with an exclusive pull-out wanted poster available only through the direct sales market. Three issues of both the mini-series (December 1992, January and February 1993) and the regular series (March, May and July 1993) were released.

The C.O.W.-Boys made their TMNT universe debut when they teamed up with the Teenage Mutant Ninja Turtles in issue #21 of the Mirage Studios title "Tales of the TMNT." The TMNT aided the C.O.W.-Boys in stopping Sheriff Terrorbull from stealing a magic crystal shard. Moo Montana and his deputies returned in number 32 of the Tales of the TMNT series. This time the horned heroes come up against Savanti Romero and the Eye of Aga-Moo-Tu. The story takes place in the astral realm of Bov-gamesh and introduces the character Tsou-T'an-Jin an ancient sorceress tortoise that lives on Moo Mesa. The C.O.W.-Boys make their third appearance with the ninja turtles in the November 2008 issue of Tales of the TMNT. The story concluded in Tales of the TMNT #58 printed in May 2009.

A special event exclusive edition of this issue was sold at a one-day event on March 31, 2007 at the Wayne Center for the Arts in Wooster, Ohio. It differs from the regular release because of its alternative cover by Andre Ponce, Ryan Brown and Steve Lavigne. It also has a special message from the arts center on the inside front cover.

In 1992, Konami released a coin-operated arcade game based on the series titled Wild West C.O.W.-Boys of Moo Mesa. The game is a side-scrolling "run 'n gun" action game similar to Konami's previous wild west-themed game Sunset Riders. Ryan Brown worked closely with Konami on the game's development.

The player characters in the game are Cowlorado Kid, Dakota Dude, Marshall Moo Montana, and a new character made for the game named Buffalo Bull. The game can be configured to allow up to four players to play simultaneously.

The game's controls consist of an eight-way joystick and two buttons for shooting and jumping. Pressing both buttons simultaneously will cause the player character to perform a stampede attack, do a spinning jump, or use any equipped item like dynamite sticks and tomahawk blades. The player can uncover a variety of power-up items by shooting flying chickens, which includes a rapid-fire Machine Gun and a Power-Up for wider bullets. Unlike Sunset Riders, the player has a three-unit life gauge that allows the player to take three hits before losing a life.

The C.O.W.-Boys of Moo Mesa make a cameo appearance in the 2003 Teenage Mutant Ninja Turtles: Fast Forward episode "Home Invasion." The Ninja Turtles visit the Tumbleweed Saloon in Moo Mesa in the form of a virtual simulation where they fight a cast of Cowtown villains and play a hand of cards with heroes Marshall Moo Montana, the Dakota Dude, and the Cowlorado Kid. The featured Moo Mesa villains are Sheriff Terrorbull, Boothill Buzzard, Shock Holiday, Big Bucks, Lone Grunger, Butch Cowsidy, Stub, and Slick Willie Weasel.